Treatment with opioid agonists and QTc prolongation: a systematic review

The aim of this paper is to review the evidence published on the relationship between opioid\r\nagonists, specifically methadone and buprenorphine and the risk of QTc interval prolongation. A literature search using the “PubMed”, “UpToDate” and “Google Scholar” databases was\r\nconducted for the years between 2005 and 2014, using the key words: “QTc”, “buprenorphine”and “methadone”. Methadone and buprenorphine are two medications widely used in the\r\ntreatment of opioid addiction. With regard to the cardiovascular risk, several studies have\r\nbeen published in recent years, with contradictory findings: some studies have reported a\r\ndose-dependent relationship between methadone dose and QTc interval prolongation, while\r\nother studies have failed to find any such relationship. The studies published over the last\r\ndecade display some major limitations: insufficient sample sizes, absence of a baseline ECG,\r\nshort follow-up or failure to assess concomitant factors that may prolong the QTc interval,\r\nsuch as other medications, illegal drugs, or potassium or magnesium plasma levels. Evidence\r\nshows an increased risk of QTc prolongation associated with methadone. Although there are\r\nfew reports exploring the relationship between buprenorphine and the QTc interval, none of\r\nthe papers reviewed detected any relationship between both. All of this warrants the need for\r\nfuture studies to overcome the limitations in the literature reviewed.